The invention concerns improved bioactive PMMA bone cements that consist of a powder component and a reactive organic liquid that, when mixed, react with one another and form a polymer-based solid material.
PMMA bone cements are clinically used primarily for attachment of joint implants. For about 50 years, they have been established in clinical practice and today are used annually in approximately 5 million cases worldwide. The chemical composition of the bone cements has practically remained unchanged throughout this time.
A deficit of bone cements that are available currently is their lack of bonding to the bone. Bone cements according to the prior art after implantation are encapsulated by a thin connective tissue layer that is the result of a mild foreign body reaction. This connective tissue layer impairs the direct force transmission between implant and bone and in the end can lead to a premature loosening of the prosthesis.
In order to improve the direct bonding of bone cement to the bone, already various approaches have been followed in the past. The goal of these approaches resides in offering calcium phosphate surfaces to the bone. Such calcium phosphate layers (in particular hydroxyl apatite) have a similar composition as natural bone material and promote therefore binding of bone cells to the bone cement. These bone cells produce then new bone substance and promote in this way intergrowth of bone cement and bone. This effect is referred to also herein (and in the scientific literature) as bioactivity of bone cement.
The approaches for providing bioactive bone cements are based currently either on the addition of bioactive substances to the bone cement, wherein some of the admixed substances may become effective on the cement surface. An alternative to this resides in producing bioactive layers on the cement surface that after implantation may be formed as deposits from the surrounding body fluid or from released substances of the bone cement. The formation of calcium phosphate layers on the surface of the cured bone cement in (simulated) body fluid or after implantation is also referred to herein as mineralization.
Known bone cements that cause mineralization of the cement surface are disclosed in Miyazaki et al. (Bioactive PMMA bone cement prepared by modification with methacryloxypropyltrimethoxysilane and calcium chloride; J. Biomed. Mater. Res. 2003, 67A(4) 1417-1423). In this connection, MPS (methacryloxypropyl trimethoxysilane) and CaCl2 are added to PMMA bone cements. The mineralization of the cement surface is achieved only at very high concentrations of additives. For a reliable mineralization in simulated body fluid within 3 days a combination of 16% CaCl2 and 20% MPS is required. Even addition of 50% MPS (without CaCl2) cause no precipitation of calcium phosphates/apatites within 14 days. This means that without calcium salt addition no mineralization occurs at all. The quantitatively high additions for mineralization also cause a significant change (worsening) of the cement properties.
U.S. Pat. No. 5,264,215 B1 discloses bone cements to which are added monomers of 4-MET (4-methacryloxyethyl trimellitic acid) or 4-META (4-methacryloxyethyl trimellitic anhydride) in combination with calcium phosphates, in particular hydroxyl apatites. These cement formulation have the disadvantage that unreacted monomer additives may reach the body. The insoluble mineral additive of calcium phosphate does not promote the mineralization.
WO 2006/122678 A2 discloses bioactive PMMA bone cements that obtain their bioactivity as a result of use of at least one of the following additives: monomers with carboxyl, sulfate, phosphate or phosphonate groups as anionic groups and at least one polymerizable unit, co-oligomers or copolymers of these monomers (that are added to the monomer liquid), water-soluble calcium salts or biocompatible buffering substances. It is the object of the present invention to provide a bioactive bone cement that after implantation forms a bioactive surface and promotes the formation of calcium phosphate phases on the cement surface and during the curing reaction and after its implantation practically cannot release any unreacted anionic monomers.
A bone cement is to be provided that with respect to preparation, handling properties, and biologic/medical properties has significant advantages. In particular, a long shelf life is to be ensured. Moreover, the use of a wider palette of anionic monomers is to be enabled. The bone cement should enable adjustment of the cement properties in a targeted fashion. Toxic effects that result from unpolymerized added monomers are to be prevented. A higher availability and effectivity of mineralization seeds on the cement surface are to be enabled. The bone cement should be compatible with all other requirements with respect to orthopedic bone cements and with all typical cement components so that the user can employ the bioactive bone cement in the same way as a conventional bone cement. Mineral components for the purpose of obtaining a bioactive cement surface should be eliminated as much as possible or completely.